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Safety Study of DS-5565 for Treatment of Fibromyalgia Pain in Subjects With Chronic Kidney Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02496884
Recruitment Status : Completed
First Posted : July 14, 2015
Last Update Posted : February 15, 2019
Sponsor:
Collaborator:
Syneos Health
Information provided by (Responsible Party):
Daiichi Sankyo, Inc.

Brief Summary:
DS-5565 (mirogabalin) is being studied as treatment for fibromyalgia (FM) pain. Because it is excreted through the kidneys, people who have reduced kidney function will not process the drug as well as with those with normal kidney function, so the dose must be reduced. This study will test two reduced dose levels for both moderately reduced and severely reduced kidney function. The study will test the hypothesis that the drug will be safe and well-tolerated in people who have both fibromyalgia and chronic kidney disease.

Condition or disease Intervention/treatment Phase
Fibromyalgia Drug: DS-5565 Drug: Placebo Phase 3

Detailed Description:

The main objective of the trial is to determine the safety and tolerability of subjects with FM and moderate to severe renal dysfunction during 13 weeks of renally-adjusted dosing of DS-5565 compared to placebo, followed by a short-term (4-week) safety follow-up.

This trial is conducted in accordance with the ethical principles of Good Clinical Practice, according to the International Council for Harmonisation (ICH) Harmonised Tripartite Guidelines. An independent Data Safety Monitoring Board (DSMB) is created to further protect the rights, safety, and well-being of subjects who participate in this study by monitoring their progress and results. The independent DSMB is composed of qualified scientists who are not investigators in the study and not otherwise directly associated with the sponsor.

Additional protection is provided by special monitoring of liver enzyme elevations and liver dysfunction performed by a Hepatic Adjudication Committee (HAC), comprised of three qualified hepatologists who are not investigators in the study and not otherwise directly associated with the sponsor. The HAC completes assessments on an ongoing basis. Adjudication of hepatic events is based on evaluation of electronic case report forms (eCRFs) and source documents, as available, including but not limited to hospital discharge summaries, diagnostic imaging, histopathology, consultation, and laboratory reports.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 56 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Placebo-controlled Safety Study of DS-5565 for Treatment of Pain Due to Fibromyalgia in Subjects With Chronic Kidney Disease
Actual Study Start Date : June 26, 2015
Actual Primary Completion Date : July 6, 2017
Actual Study Completion Date : July 6, 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: M-CKD DS-5565 7.5 mg BID
Patients with moderate chronic kidney disease (M-CKD) randomized to receive DS-5565 BID during the treatment period.
Drug: DS-5565
DS-5565 7.5 mg tablet for oral use
Other Names:
  • Experimental drug
  • Mirogabalin
  • SUB60040

Experimental: S-CKD DS-5565 7.5 mg QD
Fibromyalgia patients with severe chronic kidney disease (S-CKD) randomized to receive a DS-5565 7.5 mg tablet once per day (QD), and a placebo tablet (no drug) QD, for a total of 7.5 mg DS-5565
Drug: DS-5565
DS-5565 7.5 mg tablet for oral use
Other Names:
  • Experimental drug
  • Mirogabalin
  • SUB60040

Drug: Placebo
Placebo tablet for oral use to match DS-5565 7.5 mg tablet
Other Names:
  • No drug
  • Placebo comparator

Placebo Comparator: M-CKD Placebo
Patients with M-CKD randomized to receive placebo twice daily (BID) during the treatment period.
Drug: Placebo
Placebo tablet for oral use to match DS-5565 7.5 mg tablet
Other Names:
  • No drug
  • Placebo comparator

Placebo Comparator: S-CKD Placebo
Patients with S-CKD randomized to receive placebo once daily (QD) during the treatment period.
Drug: Placebo
Placebo tablet for oral use to match DS-5565 7.5 mg tablet
Other Names:
  • No drug
  • Placebo comparator




Primary Outcome Measures :
  1. Number of participants experiencing a Treatment Emergent Adverse Event (TEAE) [ Time Frame: baseline through follow-up period 4 weeks after the last dose of study medication, within 25 months ]

    A TEAE is any adverse event that emerges on or after the first dosing of double blind study medication and during study treatment up to 4 weeks after the last dose of double blind study medication (having been absent prior to treatment) or worsens relative to the pre-double blind treatment state. Relationship of TEAEs to study drug is assessed by the investigator.

    Clinically significant changes from baseline in clinical laboratory evaluations, neurological examinations, and electrocardiograms are reported as TEAEs.


  2. Patients Answering Yes to any question on the Columbia-Suicide Severity Rating Scale (C-SSRS) [ Time Frame: Screening, Baseline, Post-baseline (through Week 13) ]
    The C-SSRS is described as a scale developed at Columbia University that has 2-6 questions each in categories of Suicidal Ideation, Intensity of Ideation, Suicidal Behavior, and Actual Attempts. The higher the score, the higher the suicide risk.


Secondary Outcome Measures :
  1. Mean Weekly Average of Individual Daily Pain Scores (ADPS) [ Time Frame: through Week 13 ]
    Each day participants will rate their worst pain over the last 24 hours on a scale from 0-10, where 0=no pain and 10=worst pain imaginable. Each week individual pain scores will be averaged, and the mean weekly score for the treatment group will be calculated.

  2. Mean Patient Global Impression of Change (PGIC) scores [ Time Frame: at week 13 ]
    At the end of treatment, participants will rate their overall status on a scale of 1-7, where 1=very much improved and 7=very much worse using the standard PGIC questionnaire. The PGIC is a validated outcome measure for treatment of pain in the acute pain setting.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Abbreviations: alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine clearance [(CrCL) determined by the central laboratory using the Cockcroft-Gault equation], upper limit of normal (ULN), Columbia-Suicide Severity Rating Scale (C-SSRS)

Inclusion Criteria:

  • Age ≥ 18 years
  • Able to give written informed consent
  • Able to complete patient-reported questionnaires per the Investigator's judgment
  • Estimated CrCl between 15-59 mL/min from serum creatinine by the central laboratory using the Cockcroft-Gault equation
  • Fibromyalgia meeting American College of Rheumatology criteria for FM:

    • Widespread pain index (WPI) ≥ 7 and symptom severity (SS) scale score ≥ 5 or WPI 3 to 6 and SS scale score ≥ 9,
    • Pain in at least 11 of 18 specific tender point sites,
    • Symptoms have been present at a similar level for at least 3 months, and
    • The subject does not have a disorder that would otherwise explain the pain
  • Average Daily Pain Score of ≥ 4 on the 11-point numeric rating scale (NRS) over the 7 days prior to randomization (based on completion of at least 4 daily pain assessments during the 7-day baseline period prior to randomization)
  • Women of child bearing potential (WOCBP) must be using adequate methods of contraception to avoid pregnancy during the study and for 4 weeks after study completion.

Exclusion Criteria:

  • Need for ongoing use of concomitant chronic pain medications or any new non-pharmacological pain management techniques that may confound assessments of efficacy and/or safety, including neurolytic treatments (destruction of nerves by chemicals, heat, cold) or surgery, intrathecal pumps, spinal cord stimulators or psychological support within the previous year. Also excluded: topical capsaicin within 6 months; or systemic corticosteroids within 3 months of baseline period.
  • Unable to undergo pre-study washout of prohibited concomitant medications
  • Subjects with recent history (i.e., within 1 year prior to screening) of alcohol abuse or illicit drug use (cocaine, heroin, marijuana [including medical, prescribed], etc.)
  • Use of any selective serotonin reuptake inhibitor (SSRI), unless the subject has been on a stable dose for ≥ 90 days prior to screening and is not anticipated to need any dose adjustment during the course of the study
  • Subjects with severe or uncontrolled depression that, in the judgment of the Investigator, makes the subject inappropriate for entry into the study
  • Significant neurological or psychiatric disorder unrelated to neuropathic pain
  • Other severe pain (eg, sciatica, rheumatoid arthritis) that might impair the assessment of neuropathic pain
  • CrCl ≥ 60 mL/min estimated from serum creatinine by the central laboratory using the Cockcroft-Gault equation.
  • Subjects who are on hemodialysis or who require hemodialysis before the follow-up assessment; acute renal failure; history of kidney transplant
  • Any history of a malignancy other than basal cell carcinoma within the past 5 years
  • Clinically significant unstable neurologic, ophthalmologic, hepatobiliary, respiratory, or hematologic illness or unstable cardiovascular disease (eg, severe hypotension, uncontrolled cardiac arrhythmia, or myocardial infarction) within 12 months prior to screening
  • Pregnancy or breast feeding or intent to become pregnant during the study period
  • Known hypersensitivity to α2δ ligands or other components of the study medications. Note: Prior exposure to DS-5565 is allowed, as long as hypersensitivity to DS-5565 was not observed.
  • Clinically significant ECG abnormalities at the Screening Visit
  • Subjects who are at risk of suicide, as defined by their responses to the C-SSRS or in the opinion of the Investigator. Note: Subjects answering "yes" to any of the questions about active suicidal ideation/intent/behaviors that occurred within the past 12 months must be excluded (C-SSRS Suicide Ideation section - Questions 3, 4, or 5; C-SSRS Suicidal Behavior section - any of the suicide behaviors questions). Such subjects should be referred immediately to a mental health professional for appropriate evaluation.
  • Subjects who are unlikely to comply with the protocol (eg, uncooperative attitude, inability to return for subsequent visits, and/or otherwise considered by the Investigator to be unlikely to complete the study)
  • Subject is currently enrolled in, or it has been fewer than 30 days since ending, another investigational device or drug study or is receiving another investigational agent.
  • Subjects who are employees or immediate family of employees of the study site, Sponsor, or contract research organization (CRO)
  • Screening laboratory values outside the limits listed in the table below:

    • Hematology
    • Hemoglobin < 8 g/dL
    • Platelet count < 100,000/mm3
    • Absolute neutrophil count < 1,500/mm3
    • Blood chemistry
    • AST > 2.0 × ULN
    • ALT > 2.0 × ULN
    • Alkaline phosphatase > 1.5 × ULN
    • Total bilirubin > 1.2 × ULN (If a subject has total bilirubin >ULN: unconjugated and conjugated bilirubin fractions should be analyzed and only subject documented to have Gilbert's syndrome may be enrolled)
    • Creatine kinase > 3.0 × ULN
    • Calculated CrCl ≥ 60 mL/min

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02496884


Locations
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United States, Arizona
Phoenix, Arizona, United States, 85018
United States, California
Colton, California, United States, 92324
Los Angeles, California, United States, 90033
Santa Ana, California, United States, 92705
United States, Colorado
Colorado Springs, Colorado, United States, 80918
United States, Florida
Brooksville, Florida, United States, 34601
DeBary, Florida, United States, 32713
Hialeah, Florida, United States, 33013
Kissimmee, Florida, United States, 34744
Miami, Florida, United States, 33144
United States, Michigan
Grand Blanc, Michigan, United States, 48439
United States, North Carolina
High Point, North Carolina, United States, 27262
United States, Ohio
Cincinnati, Ohio, United States, 45224
United States, Pennsylvania
Wyomissing, Pennsylvania, United States, 19610
United States, South Carolina
Greer, South Carolina, United States, 29651
United States, South Dakota
Rapid City, South Dakota, United States, 57702
United States, Tennessee
Knoxville, Tennessee, United States, 37919
United States, Texas
Houston, Texas, United States, 77098
Plano, Texas, United States, 75093
United States, Washington
Bellevue, Washington, United States, 98007
United States, West Virginia
Charleston, West Virginia, United States, 25304
Morgantown, West Virginia, United States, 26505
Bulgaria
Plovdiv, Bulgaria
Sevlievo, Bulgaria
Sofia, Bulgaria
Stara Zagora, Bulgaria
Varna, Bulgaria
Czechia
Prague, Czechia
Ricany, Czechia
Hungary
Budapest, Hungary
Nyiregyhaza, Hungary
Poland
Elblag, Poland
Kraków, Poland
Romania
Cluj-napoca, Romania
South Africa
Johannesburg, South Africa
Pretoria, South Africa
Spain
Barcelona, Spain
Santiago de Compostela, Spain
Valencia, Spain
Sponsors and Collaborators
Daiichi Sankyo, Inc.
Syneos Health
Investigators
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Study Director: Global Clinical Leader Daiichi Sankyo, Inc.
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Responsible Party: Daiichi Sankyo, Inc.
ClinicalTrials.gov Identifier: NCT02496884    
Other Study ID Numbers: DS5565-A-U307
2014-003972-21 ( EudraCT Number )
First Posted: July 14, 2015    Key Record Dates
Last Update Posted: February 15, 2019
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
URL: https://vivli.org/ourmember/daiichi-sankyo/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Daiichi Sankyo, Inc.:
chronic kidney disease
. α2δ ligands
mirogabalin
pain relief
kidney metabolism
Additional relevant MeSH terms:
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Fibromyalgia
Myofascial Pain Syndromes
Kidney Diseases
Renal Insufficiency, Chronic
Urologic Diseases
Renal Insufficiency
Muscular Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Neuromuscular Diseases
Nervous System Diseases